tbuckley/cabot-search huggingface dataset:
Comparison of objective response rate and long-term overall survival in patients with treated immune checkpoint inhibitors in metastatic urothelial carcinoma.
Authors: Deniz Tural, Cagatay Arslan, Fatih Selcukbiricik, Omer Fatih Olmez, Emre Akar, Mustafa Erman, Yüksel Ürün, Dilek Erdem, Saadettin Kilickap
Journal: Journal of Clinical Oncology (2023)

481 Background: In this study, we evaluated RECIST criteria-based objective response rate (ORR) as potential surrogate endpoints for overall survival (OS) in patients who were treated with immune checkpoint inhibitors therapy (ICT) and with long-term follow-up in metastatic urothelial carcinoma. Methods: The primary endpoint was overall ORR and OS, duration of treatment (DOR) with ICT. ORR was analyzed using Fisher’s exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method. Results: The median follow-up time was 58 (1.15–71) months (mo). Progression developed in 94 (47%) patients during the first three months of treatment with ICT. The rate of complete response (CR) to ICT, partial response (PR) rate, and stable disease were 10% (n=20), 23% (n=46), and 20% (n=41), respectively. There was an imbalance in baseline characteristics between patients who had ORR and non-responder groups (Table). The 5–year OS rates for CR and PR were 73% and 23%, respectively. The median DOR for CR, PR, and SD were 51.8 mo% (44.5–59.1), 20.7mo (16.7–24.6), and 8.8 mo (5.5–12.1), respectively. Of the sixteen (80%) patients who had CR and 14 (30%) patients who had PR had an ongoing response at the time of the analysis. In univariate analysis, neutrophil-to-lymphocyte ratio (NLR) &gt;3, liver metastases, ECOG PS ≥1, and hemoglobin levels below 10 mg/dl, PR, and CR were all significantly associated with OS. In multivariate analysis, liver metastases [HR=2.3; 95% CI 1.3-4.2; p &lt; (0.004)] were independent related variable with short OS. Other hand, PR [HR=0.3; 95% CI 0.15-0.5; p &lt; (0.001)] and CR [HR=0.06; 95% CI 0.014-0.27; p &lt; (0.001)] were associated with improved OS. Conclusions: This five-year analysis of real-world data indicated a significant correlation between ORR, especially CR and OS in patients who received immune checkpoint inhibitors in metastatic urothelial cancer. Therefore, the identification of a potential surrogate marker for survival in patients treated with ICT would represent an important advance in the early identification of patients’ response or resistance to ICT.
Radical nephrectomy in medically underserved patients: Selection bias and disparity in surgical health care delivery.
Authors: Aastha Shah, Saeed Ghassemzadeh, Dhruv Puri, Margaret Meagher, Franklin Liu, Mimi Nguyen, Kevin Hakimi, Sohail Dhanji, Luke Wang, Juan Javier-Desloges, Ithaar H Derweesh
Journal: Journal of Clinical Oncology (2023)

609 Background: Disparities in outcomes of renal cell carcinoma (RCC) exist with respect to survival outcomes between different ethnic, and socioeconomic groups. We sought to evaluate disparities in delivery of surgical care between medically underserved (MU) and non-medically underserved (NMU) patients. Methods: We conducted a single-center retrospective analysis of consecutive patients presenting with localized renal cortical neoplasms who underwent surgical excision [Radical (RN) or Partial Nephrectomy (PN)] at an academic tertiary-care referral center. The cohort was divided into MU and NMU groups and descriptive analyses were conducted for demographics and clinical disease characteristics, type of surgery, time to surgery, estimated blood loss, and 30-day total and major complications (Clavien-Dindo, ≥3). Cochran-Armitage trend analysis was conducted to evaluate for surgical trends, and logistic regression multivariable analyses (MVA) were conducted for type of surgery and major complications. Results: 1418 patients were analyzed (MU n=334/NMU n=1084). Comparing MU vs. NMU, no differences were noted for age (p=0.612), Charlson Comorbidity Index (p=0.803), tumor size (p=0.236), or time to surgery (p=0.482). Significantly greater proportions of white patients were noted in NMU (60.6% vs. MU=45.5%, p&lt;0.001) and higher proportion of RN in MU (47% vs. NMU=40.4%, p=0.028). Subgroup analyses of PN groups revealed no differences with respect to demographics, tumor size (p=0.33), major complications (p=0.66), or blood loss (p=0.583). Subgroup analysis of RN revealed significantly higher proportion of non-white patients (p=0.019) and patients with diabetes (p=0.019). MVA for predictors for receipt of RN were non-white (OR1.4, p=0.002), MU (OR=1.32, p=0.043), age (OR=1.01, p=0.009) and treatment year (OR=0.913, p&lt;0.001). MVA for predictors for 30 day major complications demonstrated RN (OR=0.913 p&lt;0.001). Cochran-Armitage trend analysis indicated that both MU and NMU had significant increases in PN between 2003 and 2021 (p&lt;0.0001). Conclusions: Despite overall similarities with respect to demographics and clinical disease characteristics and time to surgery, MU status was associated with a significantly higher odds of receiving a RN at a tertiary care referral center, which represents a disparity in care and possible selection bias. Nonetheless, RN was also associated with a decreased risk of complications. While trends have demonstrated an increase in proportion of PN for both NMU and MU groups, comparative underutilization of PN in MU patients may be associated with increased downstream risks to health. Further investigation is requisite.
Impact of <sup>68</sup>Ga-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide.
Authors: Amelia Altavilla, Paola Caroli, Emilio Francesco Giunta, Emanuela Scarpi, Virginia Rossetti, Chiara Casadei, Cristian Lolli, Giuseppe Schepisi, Sara Bleve, Maria Concetta Cursano, Lorenzo Gasperoni, Federica Matteucci, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2023)

48 Background: 68 Ga prostate specific membrane antigen positron emission tomography/computed tomography ( 6 8 Ga-PSMA PET/CT) is a highly sensitive diagnostic tool to detect prostate metastatic sites even at low levels of Prostate Specific Antigen (PSA). We evaluated the impact of 68 Ga-PSMA PET/CT in patients treated with enzalutamide as first-line therapy for mCRPC. Methods: In an observational prospective study, 67 consecutive mCRPC patients were treated with enzalutamide 160 mg once daily in first-line for mCRPC. 68 Ga-PSMA PET/CT was performed at baseline, after 3 months, during follow-up and at PSA/clinical progression. Patients were evaluated on a monthly basis for serological PSA response and safety. We measured at baseline the sum of metabolic total volume (SMTV), mean standardized uptake volume (SSUVmean), maximum standardized uptake volume (SSUVmax) and total lesion activity (STLA), which is the product of SMTV and SSUVmean, for a maximum of 20 lesions. These parameters together with baseline PSA level, Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason Score (GS) and age were analyzed by univariate and multivariate Cox regression models as potential predictors of progression-free survival (PFS) and overall survival (OS). Results: At the moment of the present analysis, 58 mCRPC patients were considered fully evaluable. The median age was 75 years (range, 47-91), ECOG PS was 0 in 47 cases (81%), 1-2 in 11 (19%), GS was &lt;8 in 22 (38%), 8-10 in 36 (62%), the median baseline PSA was 2.66 µg/L (range 0.09-197). We observed a median SMTV of 5.73 cm 3 , median SSUVmax of 44.85, median SSUVmean of 25.80 and median STLA of 59.66. At the median follow-up of 52 months, median PFS was 28.9 months (95% CI 16.3-43.6), median OS was not reached (95% CI 36.8-not reached). In univariate analysis, SSUVmax and STLA were significant for PFS (p=0.015 and p=0.001, respectively) and OS (p=0.026 and p=0.019, respectively), while SSUVmean was significant only for OS (p=0.028). On multivariate analysis, STLA only remained significant for PFS (p&lt;0.001) and OS (p=0.026). Conclusions: The assessment of mCRPC by 68 Ga-PSMA PET/CT before starting enzalutamide was associated with longer median PFS and OS compared to prior studies using standard imaging only. STLA, expression of both volume and intensity of 68 Ga-PSMA uptake, appeared the strongest parameter able to predict PFS and OS.
Patient (pt) perspective on fatigue and its management for advanced prostate cancer (PC) treated with androgen receptor inhibitors (ARIs).
Authors: Stephen J. Freedland, Marty Chakoian, Edward Wells, Nader N. El-Chaar, Alexandra Colon, Dina Elsounda, Agnes Hong
Journal: Journal of Clinical Oncology (2023)

100 Background: Fatigue is a common, multifaceted disease- and treatment (tx)-related symptom experienced by pts with advanced PC (aPC). Although fatigue of variable severity has been reported across clinical trials in pts with metastatic hormone-sensitive PC (also referred to as metastatic castration-sensitive PC [mCSPC]) and non-metastatic castration-resistant PC (nmCRPC) treated with ARIs, there is limited real-world insight from the pt’s perspective or guidance on the management of this symptom. This study assessed pts’ experience with fatigue and self-reported management strategies. Methods: In this cross-sectional non-interventional qualitative research study, pts receiving ARIs were interviewed about their fatigue experience and management strategies. All pts were ≥18 years, diagnosed with mCSPC or nmCRPC, currently on ARI tx (enzalutamide, apalutamide or darolutamide) that began ≤24 months (mo) prior to interview and experienced fatigue. Descriptive data extracted were organized into general concepts and presented as number and frequency of reports. Results: Among 143 screened pts, 11 completed the interview (mCSPC, 7; nmCRPC, 4). Most were White, mean age was 63 years and median time since ARI initiation was 12 mo. Pts described their fatigue experience as a physical, emotional or mental feeling that impacted activities of daily living. Pts attributed their fatigue to more than one cause including, but not limited to: a side effect of ARI tx, emotional burden of disease, or physical exertion. Most pts did not feel adequately prepared and indicated they would have liked to receive additional education or support to manage tx-related fatigue. As a result, most pts followed self-initiated management strategies such as healthy diet, rigorous exercise and increased rest, which were reported to be effective for some pts. Conclusions: Pts with aPC emphasized the lack of adequate knowledge and health care provider (HCP) recommendations for managing fatigue. Hence, there is a need to develop recommendations for fatigue management and resources to support HCPs’ counselling methods to ultimately improve pts’ quality of life while on tx. HCPs may play a critical role in developing and disseminating fatigue management initiatives. [Table: see text]
Real-world treatment and quality of life (QOL) in locally advanced or metastatic urothelial carcinoma (la/mUC) in Saudi Arabia, Singapore, South Korea, Taiwan, and Turkey.
Authors: Li-Jen Cheng, Janet Kim, Apurba Mukherjee, Neil Milloy, Mia Unsworth, Daniel Ng
Journal: Journal of Clinical Oncology (2023)

462 Background: Little is known about treatment and QOL of la/mUC in Saudi Arabia, South Korea, Turkey, and Taiwan. Therefore, this study assessed patient (pt), tumor, and disease characteristics; treatment sequencing; and QOL in pts with la/mUC treated in these countries. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world, multinational, point-in-time study using validated methodology (Anderson et al. Curr Med Res Opin. 2008;24:3063-72) and included physician surveys, chart reviews, and pt questionnaires (Saudi Arabia, Turkey, and Taiwan only). Data were collected (12/2021–3/2022) from oncologists and urologists and adult pts with confirmed la/mUC. EQ-5D visual analogue scale (VAS; scores: 0 [worst health] to 100 [best health]) and the global health status (QL2) from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (scores: 0 [low functioning] to 100 [high functioning]) questionnaires were used to assess QOL. Results: Data were provided by 175 physicians for 988 pts (Turkey, n=300; Saudi Arabia, n=240; South Korea, n=298; Taiwan, n=150) with la/mUC. Mean pt age was 66.3 y; 77% were men. Most (77%) pts had no family history of urothelial carcinoma (UC); 30% recorded no risk factors (eg, genetic risk, smoking, occupational exposure). At initial UC diagnosis, the bladder was the initial tumor location in 82% of pts, of whom 67% had la/mUC, and 83% of pts had an Eastern Cooperative Oncology Group performance status 0–2. At data collection, the most common metastatic sites were the lymph nodes (53%), lungs (29%), liver (27%), and bone (21%). Biomarker/tumor testing was not done in 45% of pts. In pts initially diagnosed with nonmetastatic UC (n=346), 28% received neoadjuvant and 31% received adjuvant therapy. Of pts receiving ≥1 line of therapy (LOT) for la/mUC (n=988), 74% received gemcitabine, 60% received cisplatin, 18% received carboplatin, 17% received a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor, and 4% received best supportive care (BSC) in the first-line (1L) setting; mean duration of therapy (DOT) in 1L was 5.7 mo. Of pts receiving ≥2 LOTs for la/mUC (n=290), 63% received a PD-1/L1 inhibitor and 35% received chemotherapy in the second-line (2L) setting; mean DOT in 2L was 4.9 mo. Of pts receiving ≥3 LOTs for la/mUC (n=87), 59% received chemotherapy (most often cisplatin [46%] or gemcitabine [38%]), 34% received a PD-1/L1 inhibitor, and 10% received BSC only in the third-line (3L) setting; mean DOT in 3L was 4.3 mo. Questionnaires were available for 319 pts. Mean (SD) EQ-5D VAS score was 51.8 (15.6); EORTC QL2 score was 44.6 (19.9). Conclusions: Pts with la/mUC in this multinational study generally received 1L platinum-based and 2L PD-1/L1 inhibitor therapies. These results highlight the need for therapies that improve clinical and QOL outcomes.
Efficacy and safety of darolutamide (DARO) in combination with androgen-deprivation therapy (ADT) and docetaxel (DOC) by disease volume and disease risk in the phase 3 ARASENS study.
Authors: Maha H. A. Hussain, Bertrand F. Tombal, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Neal D. Shore, Evgeny Kopyltsov, Arash Rezazadeh, Martin Boegemann, Ding-Wei Ye, Felipe Melo Cruz, Hiroyoshi Suzuki, Shivani Kapur, Shankar Srinivasan, Frank Verholen, Iris Kuss, Heikki Joensuu, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2023)

15 Background: In ARASENS (NCT02799602), DARO plus ADT and DOC significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI: 0.57–0.80; P&lt;0.0001) vs placebo (PBO) + ADT + DOC in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC), with similar overall incidences of treatment-emergent adverse events (TEAEs) between groups. The effect of DARO on overall survival (OS) was consistent across prespecified subgroups, including de novo and recurrent disease. For pts with mHSPC, outcomes based on disease volume and risk provide additional information to clinicians. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO, with ADT + DOC. High-volume disease was defined as visceral metastases and/or ≥4 bone metastases with ≥1 beyond the vertebral column/pelvis (CHAARTED criteria). High-risk disease was defined as ≥2 risk factors: Gleason score ≥8, ≥3 bone lesions, and presence of measurable visceral metastasis (LATITUDE criteria). OS for these subgroups was assessed using an unstratified Cox regression model. Results: Of 1305 pts in the full analysis set, 1005 (77%) had high-volume disease, 912 (70%) had high-risk disease, 300 (23%) had low-volume disease, and 393 (30%) had low-risk disease. DARO + ADT + DOC prolonged OS regardless of high- or low-volume disease with HRs of 0.69 and 0.68 vs PBO + DOC + ADT, respectively. OS benefit of DARO vs PBO was also similar for pts with high- or low-risk disease. DARO improved clinically relevant secondary endpoints vs PBO in high/low-volume and risk subgroups, with HRs generally in the range of those observed in the overall population. Incidences of TEAEs were consistent with the overall ARASENS population across subgroups by high/low volume and high/low risk. Conclusions: In pts with mHSPC, the benefits of early treatment intensification with DARO + ADT + DOC on OS and key pt-relevant secondary efficacy endpoints vs PBO + ADT + DOC were similar in patients with high- and low-volume as well as high- and low-risk mH+SPC. The favorable safety profile of DARO was reconfirmed in high/low-volume and high/low-risk populations. DARO + ADT + DOC sets a new standard of care for pts with mHSPC. Clinical trial information: NCT02799602 . [Table: see text]
Characterization of lymph node metastases in prostate cancer.
Authors: Josh Gottlieb, Jane Choe, Shu-Ching Chang, David Krasne, Dave S. B. Hoon, Timothy Wilson
Journal: Journal of Clinical Oncology (2023)

380 Background: Unlike lymph node (LN) staging in other malignancies, prostate cancer nodal staging does not characterize or quantify the LN tumor burden. Detailed characterization of LN metastases may provide improved prognostic information, which could assist in post-surgical management decisions. Methods: Clinical and pathologic information was retrospectively collected via electronic medical record from 66 patients with pathologically confirmed LN involvement after radical prostatectomy with pelvic lymph node dissection performed by a single surgeon. Tissue slides of all positive LNs were re-evaluated by a single pathologist in accordance with our institutional review board protocol. Poisson regression analyses and Cox proportional-hazard regression were performed to evaluate the association of risk factors with the number of positive nodes and the association of LN characteristics with biochemical recurrence (BCR)-free survival. Results: Median number of positive LNs per patient was 2 (IQR 1-3). Mean % positive LNs per patient was 8.9 (SD10.4). Mean cumulative size of all tumor deposits in all positive LNs per patient was 5.0mm (SD 4.8). Average % surface area of LN involved by tumor was 28%. 48 (73%) patients were alive without disease at median follow-up time of 38 months (IQR 26-50 months). Higher pre-surgery PSA, clinical stage T3-T4 versus T1-2, extraprostatic extension (EPE), seminal vesical involvement (SVI), and lymphovascular invasion (LVI) were significantly associated with higher incidence rate of nodal positivity. Larger mean size of largest LN deposits, mean size of total LN deposits, and mean % surface area of LN involved were significantly associated with worse BCR-free survival. There was no significant association for number of positive nodes, LN anatomical compartments, extranodal extension (ENE), span of ENE, and distance of ENE from LN capsule. Higher pre-surgery PSA and post-surgery Gleason grade were significantly associated with worse BCR-free survival. Conclusions: Our data shows that LN tumor burden is associated with worse BCR-free survival. Anatomical LN compartments and quantification of ENE did not show significant association with BCR. [Table: see text]
Adherence to standard of care (SOC) therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC): A single-institution analysis.
Authors: Puneet Dhillon, Moshe Chaim Ornstein, Shilpa Gupta, Amanda Nizam, Timothy D. Gilligan, Allison Martin, Amanda Bonham, Kimberly Maroli, Christopher Eing Wee
Journal: Journal of Clinical Oncology (2023)

103 Background: Androgen deprivation therapy (ADT) has been the backbone of treatment for mHSPC for decades. In recent years, multiple randomized controlled trials demonstrating an overall survival (OS) benefit of combination treatment (e.g. ADT + novel hormonal agent and/or chemotherapy) has made this the current SOC. Large real-world reports have shown a significant number of patients are still being treated below the SOC with ADT alone, but these databases do not include patient level data to help understand the rationale for treatment decisions. We reviewed our institution’s treatment patterns for mHSPC to better understand why some patients are being treated with ADT alone. Methods: We conducted a retrospective analysis on patients who initiated treatment for mHSPC from 2017-2021 at Cleveland Clinic. Patient characteristics were recorded, including age and histology. Treatment characteristics, including location of treatment, treatment regimen, and treatment rationale (if not treated with SOC) were noted. Results: Four hundred forty-nine patients were included, with diagnosis of metastatic disease made at a median of 63 years, of which 446 started treatment with systemic therapy. The vast majority of patients were managed by a medical oncologist (95.5%). About half of the patients (49.8%) received treatment at the main campus, with the remaining patients being treated at an affiliated regional hospital (28.7%) or outpatient medical center (21.5%). Additional characteristics are shown. Out of the 446, 40 (9.0%) patients received ADT alone. Reasons for ADT monotherapy included patient preference (n = 13), cost (n = 2), and poor functional status/comorbidities (n = 4). Twenty (50%) of the patients who got ADT alone had no documented rationale for why this treatment plan was elected. One patient was lost to follow-up. For patients who received only ADT, 12 were treated at main campus, 20 were treated at a regional hospital, and 8 were treated at an outpatient medical center. Conclusions: At our institution, adherence to treatment up to SOC for mHSPC was better than previous real-world reports. There were documented reasons for not treating mHSPC up to SOC combination therapy for half of the patients who got ADT monotherapy. It remains unclear why the remaining half did not get combination therapy up to the SOC. [Table: see text]